Cereto-Massague A.,Rovira i Virgili University | Ojeda M.J.,Rovira i Virgili University | Valls C.,Rovira i Virgili University | Mulero M.,Rovira i Virgili University | And 4 more authors.Methods | Year: 2015

Martinez-Fernandez L.,Rovira i Virgili University | Pons Z.,Rovira i Virgili University | Margalef M.,Rovira i Virgili University | Arola-Arnal A.,Rovira i Virgili University | And 2 more authors.Journal of Nutritional Biochemistry | Year: 2015

Thiazolidinediones (TZDs), such as rosiglitazone and pioglitazone, are peroxisome proliferator-activated receptor (PPAR) full agonists that have been widely used in the treatment of type 2 diabetes mellitus. Despite the demonstrated beneficial effect of reducing glucose levels in the plasma, TZDs also induce several adverse effects. Consequently, the search for new compounds with potent antidiabetic effects but fewer undesired effects is an active field of research. Interestingly, the novel proposed mechanisms for the antidiabetic activity of PPAR agonists, consisting of PPAR Ser273 phosphorylation inhibition, ligand and receptor mutual dynamics, and the presence of an alternate binding site, have recently changed the view regarding the optimal characteristics for the screening of novel PPAR ligands. Furthermore, transcriptional genomics could bring essential information about the genome-wide effects of PPAR ligands. Consequently, facing the new mechanistic scenario proposed for these compounds is essential for resolving the paradoxes among their agonistic function, antidiabetic activities, and side effects and should allow the rational development of better and safer PPAR-mediated antidiabetic drugs.

PubMed | Rovira i Virgili University, Avinguda University and University of the Balearic IslandsType: Comparative Study | Journal: The British journal of nutrition | Year: 2015

Diet during pregnancy and lactation is a critical factor in relation to the health of dams and their offspring. Currently, control diets used in metabolic imprinting studies differ in composition and type, i.e. semi-purified diets (SD) or chow-based diets (ND). The aim of the present study was to determine whether two widely used control diets, a SD and a ND, that mainly differ in fat content (508 and 326%, respectively) and its sources (soyabean oil for the SD and cereals and fish for the ND), fibre (6 and 15%, respectively), and cholesterol (26 and 69mg/kg diet, respectively) can influence the lipid metabolism of dams and their offspring. Wistar rats were fed either the SD or the ND during pregnancy and lactation. At weaning, SD-fed dams presented severe hepatic steatosis and increased levels of circulating TAG, NEFA and insulin. Importantly, the offspring presented an altered plasma lipid profile. In contrast, the ND allowed for a normal gestation and lactation process, and did not affect the metabolism of offspring. In parallel, virgin rats fed the SD showed no metabolic alterations. A higher intake of SFA and MUFA and a lower consumption of PUFA observed in SD-fed dams during the lactation period could contribute to explaining the observed effects. In conclusion, two different control diets produced very different outcomes in the lipid metabolism of lactating rats and their offspring. The present results highlight the importance of the assessment of the metabolic state of dams when interpreting the results of metabolic programming studies.